OSMI-4
目录号 : GC31517
OSMI-4 是迄今为止报道的最好的 OGT 抑制剂，OSMI-4 的活性形式具有低纳摩尔结合亲和力。
Cas No.:2260791-14-6
Sample solution is provided at 25 µL, 10mM.
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OSMI-4 is the best OGT inhibitor reported to date and the active form of OSMI-4 has low nanomolar binding affinity [1]. OSMI-4 has a chlorine substituent on the quinolinone ortho to the sulfonamide, thus allowing the molecule to bind tighter in the uridine binding pocket within the enzyme’s active site [2]. The free acid and ester forms of OSMI-4 are OSMI-4a and OSMI-4b, respectively.
OSMI-4 has further enhanced binding affinities to the enzyme with a Kd of 8 nM. The IC50 of OSMI-4a and OMSI-4b are 1.5 and 0.5μM, respectively [3]. The EC50 of OSMI-4 in HEK293T cells is 3 μM [1].
References:
[1].Martin SES, Tan ZW, Itkonen HM, Duveau DY, Paulo JA, Janetzko J, Boutz PL, T?rk L, Moss FA, Thomas CJ, Gygi SP, Lazarus MB, Walker S. Structure-Based Evolution of Low Nanomolar O-GlcNAc Transferase Inhibitors. J Am Chem Soc. 2018 Oct 24;140(42):13542-13545.
[2].Ju Kim E. O-GlcNAc Transferase: Structural Characteristics, Catalytic Mechanism and Small-Molecule Inhibitors. Chembiochem. 2020 Nov 2;21(21):3026-3035.
[3].Loi EM, Weiss M, Pajk S, Gobec M, Toma?i? T, Pieters RJ, Anderluh M. Intracellular Hydrolysis of Small-Molecule O-Linked N-Acetylglucosamine Transferase Inhibitors Differs among Cells and Is Not Required for Its Inhibition. Molecules. 2020 Jul 25;25(15):3381.
OSMI-4 是迄今为止报道的最好的 OGT 抑制剂，OSMI-4 的活性形式具有低纳摩尔结合亲和力[1]。 OSMI-4 在与磺酰胺邻位的喹啉酮上有一个氯取代基，因此允许该分子在酶活性位点 [2] 内的尿苷结合袋中更紧密地结合。 OSMI-4的游离酸和酯形式分别为OSMI-4a和OSMI-4b。
OSMI-4 进一步增强了对该酶的结合亲和力，Kd 为 8 nM。 OSMI-4a和OMSI-4b的IC50分别为1.5和0.5μM[3]。 OSMI-4在HEK293T细胞中的EC50为3 μM [1]。
| Kinase experiment [1]: | |
|
Preparation Method |
OGT reactions were carried out in a 50-µL final volume, containing 0.1 mM UDP-GlcNAc, 200 nM purified full-length OGT, OSMI-4a/b,100 µM RBL-2 peptide in OGT reaction buffer. Reactions were incubated at 37℃ for 2 h. Afterwards, each reaction was transferred in duplicate into a 96-well white microplate and was mixed with a 1:1 ratio of the UDP-Glo Detection Reagent. After incubation at room temperature for 1 h, the luminescence was recorded with a POLARstar® Omega microplate reader or with a BioTek Synergy™ H4 microplate reader. |
|
Reaction Conditions |
37℃ for 2 h |
|
Applications |
IC50 of OSMI-4a and OMSI-4b are 1.5 and 0.5μM, respectively. |
| Cell experiment [2]: | |
|
Cell lines |
HEK293T |
|
Preparation Method |
Cells were plated and grown in their respective media until they reached a confluency of 60-80%. For HEK293T cells, media was changed 3 hours before OSMI-4 was added; OSMI-4 was added directly to each well at the indicated concentrations. The number of dead cells were assessed by CellToxTM Green cytotoxicity Assay. |
|
Reaction Conditions |
0.125,0.25,0.5,1,2,4,8,16μM，24 h |
|
Applications |
EC50 of OSMI-4 in cells is 3 μM |
|
References: [1]. Loi EM, Weiss M, Pajk S, Gobec M, Tomašič T, Pieters RJ, Anderluh M. Intracellular Hydrolysis of Small-Molecule O-Linked N-Acetylglucosamine Transferase Inhibitors Differs among Cells and Is Not Required for Its Inhibition. Molecules. 2020 Jul 25;25(15):3381. [2]. Martin SES, Tan ZW, Itkonen HM, Duveau DY, Paulo JA, Janetzko J, Boutz PL, Törk L, Moss FA, Thomas CJ, Gygi SP, Lazarus MB, Walker S. Structure-Based Evolution of Low Nanomolar O-GlcNAc Transferase Inhibitors. J Am Chem Soc. 2018 Oct 24;140(42):13542-13545. |
|
| Cas No. | 2260791-14-6 | SDF | |
| Canonical SMILES | O=C1C=CC2=C(C=C(Cl)C(S(N[C@@H](C(N(CC(OCC)=O)CC3=CC=CS3)=O)C4=C(OC)C=CC=C4)(=O)=O)=C2)N1 | ||
| 分子式 | C27H26ClN3O7S2 | 分子量 | 604.09 |
| 溶解度 | DMSO : 125 mg/mL (206.92 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.6554 mL | 8.2769 mL | 16.5538 mL |
| 5 mM | 0.3311 mL | 1.6554 mL | 3.3108 mL |
| 10 mM | 0.1655 mL | 0.8277 mL | 1.6554 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet